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Biosensors based on silicon nanowires (Si-NWs) promise highly sensitive dynamic label-free electrical detection of biomolecules. Despite the tremendous potential and promising experimental results, the fundamental mechanism of electrical sensing of biomolecules and the design considerations of NW sensors remain poorly understood. In this paper, we discuss the prospects and challenges of biomolecule detection using Si-NW biosensors as a function of device parameters, fluidic environment, charge polarity of biomolecules, etc., and refer to experimental results in literature to support the nonintuitive predictions wherever possible. Our results indicate that the design of Si nanobiosensor is nontrivial and as such, only careful optimization supported by numerical simulation would ensure optimal sensor performance.